Genetic and epigenetic etiology of autoimmune diseases: lessons from twin studies

Abstract

Twin studies have been considered as strong approaches in determining the cause of complex diseases with regard to identifying the involvement of multiple genes, single genes, environmental factors, and a possible relation between genetics and the environment. The concordance observed among monozygotic (MZ) twins suggests the involvement of genetic factors. Nonetheless, MZ twins demonstrate a rate of discordance in different characteristics, like proneness towards diseases, despite virtually identical genetic backgrounds. Discordance has been suggestive of the involvement of the environment alongside genetic factors. As a result, a bulk of studies has supported the hypothesis that environmental factors can impress the epigenetic construction and, therefore, influence disease susceptibility. Twin studies yield data about clinical courses and outcomes of disease, in addition to knowledge of genetics, epigenetics, environmental factors, and risk of disease development. To date, genome-wide association studies (GWASs) have reported that genomic variants are responsible for only a number of cases of autoimmunity in twins and have been unable to explain the disease discordance among MZ twins. With respect to the exploration of epigenetic mechanisms in autoimmunity, discordant MZ twins have been attractive models and have contributed remarkably. It is essential for future studies to evaluate the genetic variants as well as epigenetic changes in large twin populations. The current review discusses the genetic and epigenetic lessons obtained from studies of twin cases.